Bioerodible polymers used to control the release of therapeutic agents physically dispersed in the polymer matrix have been described in a variety of contexts. One matrix which has been successful is a family of poly(ortho esters). These materials contain the pH-sensitive ortho ester linkage in their polymer backbone. Such polymers are described, for example, in U.S. Pat. No. 4,304,767 to Heller et al. Because the ortho ester linkages within these polymers are relatively stable at neutral pH, and hydrolyze progressively faster with the decreasing pH of the surrounding medium, the rate of erosion of the polymer can be manipulated within a very wide range by incorporating various levels and strengths of acidic excipients into the polymer matrix.
The method of preparing polymers according to the aforementioned patent comprises the addition of polyols to diketene acetals as shown in Scheme 1. ##STR1## Using this scheme, almost any diketene acetal and any diol can be used, and the synthetic method is thus extremely versatile. Polymers synthesized by this method are, however, not optimal for preparing soft or amorphous drug dosage forms such as bioerodible ointments, creams or gels due to the relatively rigid pentaerythritol segment in the polymer backbone.
There is a need in the art for a bioerodible composition which has a molecular structure of sufficient flexibility to enable its use as a bioerodible matrix in soft dosage forms such as ointments, gels, creams, or the like. An ideal material would enable the topical delivery of an effective dose level of pharmaceutical agent from an ointment or the like at a desired rate for a period of time dictated only by clinical considerations and not by limitations of the ointment, cream or gel formulation. The ability to achieve this is particularly important in cases where excessive and uncontrolled application of a drug can produce serious side effects.